Derivative of oxyarylarsinic acids and process of making same.



UNITED STATES PATENT OFFICE.

PAUL EHRLICH. AND ALFRED BERTHEIM, OF FRANKFOBT-ON THE-MAIN, GERIEANY,

ASSIGNORS TO FARBWERKE VORM. MEISTER LUCIUS & BBI l'NING, OF HOGHST-ON- THE-MAIN, GERIVIANY, A CORPORATION OF GERMANY.

DERIVATIVE OF OXYARYLARSINIC ACIDS AND PROCESS OF MAKING SAME.

No Drawing.

To all whom/it may concern:

Be it known that we, PAUL EHRLIGH, M. D., professor of medicine, and ALFRED BERTHEILflPh.D.,CltlZe11S of the Empire of Germany, residing at Frankfort-on-the-Main,

Germany, have invented certain new and derivatives of the oxyarylarsinic acids by reduction, are valuable products, as they are a specific therapeutic agent for curing syphilis and febris recurrens. The said new aminooxy derivatives of arsenobenzene are yellow powders which are insoluble or 'diflicultlysoluble in water and the usual or garlic solvents; they melt with decomposition and dissolve in alkalis as well as in dilute mineral acids forming salts; their alkaline solution is altered on exposure to the air. The process may, for instance, be illustrated by the following equation:

eogasmoi) onmsoum+mrn= cemmmxomaseis remain) (OH)+10H1O.

For therapeutical purposes they may be.

administered, for instance, by injecting subcutaneously. 0.3 g. of the sodium salt of diaminodioxyarsenobenzene.

The procedure for preparing the new compounds may, for instance, be as follows: 144: g. of sodium para-oxyphenylarsinate, dried at 80 (1., are introduced by portions into 450 com. .of concentrated sulfuric acid at 0 C. while well stirring. Into this mass a mixture of 239.com. of nitric acid (specific gravity 1.4:) and 39 com. of concentrated sulfuric acid is poured by drops, while continuing the stirring, taking care that the temperature does not rise over 0 C. The stirring is continued and the temperature allowed to rise to about 10 C. After some hours, the mass is poured into 2250 com. of

.Water and the nitrooxyphenylarsinic acid which crystallizes slowly from the solution may be filtered off. It forms a yellowishwhite crystalline powder. This nitro6xyphenylarsinic acid is pretty readily soluble in hot water, but diflicultly soluble in cold water, readily soluble in alcohol, acetone of glacial acetic acid. Its alkaline salts, which Specification of Letters Patent. Application filed May 9, 1910. Serial No. 560,271.

, Patented Mari 7, 1911.

(Specimens) are readily .soluble in water, are of a highyellow color; it decomposes when heated. 66 g. of nitrooxyphenylarsinic acid are dissolved in 1320 com. of water and 225 com. ofcaustic soda lye of twice the normal strength and thenintroduced into a solution of 855 g. of anhydrous sodium hydrosulfite and 171 g. of crystallized magnesium chlorid in 4275 ccm. of water. The magnesium chlorid is added for the purpose of keeping neutral the reaction of the solution, as this gives the most advantageous condition in the process. On digesting the solution at 0., a light-yellow, microcrystalline precipitate separates which consists of the diaminodioxyarsenobenzene. Its separation is completed by. gently heating for some time. When filtered off and dried, the new compound forms a yellow powder which is solu ble in dilute hydrochloric acid and in caustic soda lye and carbonate of soda; from such an alkaline solution is may be again separated by an addition of acetic acid. The diaminodioxyarsenobenzene is nearly insoluble in water and the usual organic solvents such as alcohol, ether, benzene; it decomposes when heated at about 165 0. Its dihydrochlorid, which may be precipitated from amethyl-alcoholic solution by ether, is a light yellow powder, readily soluble in water and -methyl-alcohol, scarcely soluble in ethyl-alcohol,insoluble inether or ben- 190 C. In an analogous manner there may,

for instance, be produced from dinitrooxyphenylarsinic acid the tetraminodioxyarsenobenze'ne and from nitro orthocresolarsinic acid the diaminodioxyarsenotoluene, which compounds possess properties similar to those of the diaminodioxyarsenobenzene.

Having now particularly described our invention, what we claim is:

1. As new products, aminooxyarsenobenzenes, being" derivatives of the paraparadioxyarsenobenzene, which are yellow pow-- ders insoluble or difiicultly soluble in water and the usual organic solvents, melting with decomposition, and forming with alkalis or dilute mineral acids soluble salts. 2. As a new product, diaminodioxyarsenobenzene, being a yellow powder, insoluble in water, alcohol, ether and benzene, readily dissolving in caustic soda lye and dilute hydrochlori'ci acid, d decomP0sing...when""' heated to about 165 (1.; said product being,

decomposing when heated at about 190 C.

3. The process of manufacturing new arsenical remedies, which consists in treating nitro'oxyarylarsinic acids With a strong reducing agent, as hereinbefore described.

4. The process of manufacturing new arsenical remedies, Which consists in treating nitro-para-oxyphenylarsinic acid With a nitro-para-oxyphenylarsinic acid With a hydrosulfite, as hereinbefore described.

In testimony whereof, We aflix our signatures in presence of two Witnesses.

PAUL EHRLICH. ALFRED BERTHEIM.

Witnesses:

JEAN GRUND, CARL GRUND. 

